PMID- 24658422 OWN - NLM STAT- MEDLINE DCOM- 20141118 LR - 20240322 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 9 IP - 3 DP - 2014 TI - Brain-derived neurotrophic factor/FK506-binding protein 5 genotype by childhood trauma interactions do not impact on hippocampal volume and cognitive performance. PG - e92722 LID - 10.1371/journal.pone.0092722 [doi] LID - e92722 AB - In the development of psychotic symptoms, environmental and genetic factors may both play a role. The reported association between childhood trauma and psychotic symptoms could therefore be moderated by single nucleotide polymorphisms (SNPs) associated with the stress response, such as FK506-binding protein 5 (FKBP5) and brain-derived neurotrophic factor (BDNF). Recent studies investigating childhood trauma by SNP interactions have inconsistently found the hippocampus to be a potential target underlying these interactions. Therefore, more detailed modelling of these effects, using appropriate covariates, is required. We examined whether BDNF/FKBP5 and childhood trauma interactions affected two proxies of hippocampal integrity: (i) hippocampal volume and (ii) cognitive performance on a block design (BD) and delayed auditory verbal task (AVLT). We also investigated whether the putative interaction was different for patients with a psychotic disorder (n = 89) compared to their non-psychotic siblings (n = 95), in order to elicit possible group-specific protective/vulnerability effects. SNPs were rs9296158, rs4713916, rs992105, rs3800373 (FKBP5) and rs6265 (BDNF). In the combined sample, no BDNF/FKBP5 by childhood trauma interactions were apparent for either outcome, and BDNF/FKBP5 by childhood trauma interactions were not different for patients and siblings. The omission of drug use and alcohol consumption sometimes yielded false positives, greatly affected explained error and influenced p-values. The consistent absence of any significant BDNF/FKBP5 by childhood trauma interactions on assessments of hippocampal integrity suggests that the effect of these interactions on psychotic symptoms is not mediated by hippocampal integrity. The importance of appropriate statistical designs and inclusion of relevant covariates should be carefully considered. FAU - Hernaus, Dennis AU - Hernaus D AD - Department of Psychiatry and Psychology, South Limburg Mental Health Research and Teaching Network, EURON, School for Mental Health and NeuroScience MHeNS Maastricht University, Maastricht, The Netherlands. FAU - van Winkel, Ruud AU - van Winkel R AD - Department of Psychiatry and Psychology, South Limburg Mental Health Research and Teaching Network, EURON, School for Mental Health and NeuroScience MHeNS Maastricht University, Maastricht, The Netherlands; University Psychiatric Centre Catholic University Leuven, Kortenberg, Belgium. FAU - Gronenschild, Ed AU - Gronenschild E AD - Department of Psychiatry and Psychology, South Limburg Mental Health Research and Teaching Network, EURON, School for Mental Health and NeuroScience MHeNS Maastricht University, Maastricht, The Netherlands. FAU - Habets, Petra AU - Habets P AD - Department of Psychiatry and Psychology, South Limburg Mental Health Research and Teaching Network, EURON, School for Mental Health and NeuroScience MHeNS Maastricht University, Maastricht, The Netherlands. FAU - Kenis, Gunter AU - Kenis G AD - Department of Psychiatry and Psychology, South Limburg Mental Health Research and Teaching Network, EURON, School for Mental Health and NeuroScience MHeNS Maastricht University, Maastricht, The Netherlands. FAU - Marcelis, Machteld AU - Marcelis M AD - Department of Psychiatry and Psychology, South Limburg Mental Health Research and Teaching Network, EURON, School for Mental Health and NeuroScience MHeNS Maastricht University, Maastricht, The Netherlands. FAU - van Os, Jim AU - van Os J AD - Department of Psychiatry and Psychology, South Limburg Mental Health Research and Teaching Network, EURON, School for Mental Health and NeuroScience MHeNS Maastricht University, Maastricht, The Netherlands; King's College London, King's Health Partners, Department of Psychosis Studies, Institute of Psychiatry, London, United Kingdom. FAU - Myin-Germeys, Inez AU - Myin-Germeys I AD - Department of Psychiatry and Psychology, South Limburg Mental Health Research and Teaching Network, EURON, School for Mental Health and NeuroScience MHeNS Maastricht University, Maastricht, The Netherlands. FAU - Collip, Dina AU - Collip D AD - Department of Psychiatry and Psychology, South Limburg Mental Health Research and Teaching Network, EURON, School for Mental Health and NeuroScience MHeNS Maastricht University, Maastricht, The Netherlands. CN - for Genetic Risk and Outcome in Psychosis (G.R.O.U.P.) LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140321 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Brain-Derived Neurotrophic Factor) RN - EC 5.2.1.- (Tacrolimus Binding Proteins) RN - EC 5.2.1.8 (tacrolimus binding protein 5) SB - IM MH - Adult MH - Brain-Derived Neurotrophic Factor/*genetics MH - *Cognition MH - Female MH - *Genotype MH - Hippocampus/*pathology MH - Humans MH - Magnetic Resonance Imaging MH - Male MH - Neuropsychological Tests MH - Organ Size MH - Polymorphism, Single Nucleotide MH - Psychotic Disorders/*diagnosis/drug therapy/*etiology MH - Risk Factors MH - Tacrolimus Binding Proteins/*genetics MH - Tomography, X-Ray Computed MH - Young Adult PMC - PMC3962453 COIS- Competing Interests: Co-authors Inez Myin-Germeys and Jim van Os are PLOS ONE Editorial Board members. This does not alter the authors' adherence to PLOS ONE Editorial policies and criteria. EDAT- 2014/03/25 06:00 MHDA- 2014/11/19 06:00 PMCR- 2014/03/21 CRDT- 2014/03/25 06:00 PHST- 2013/12/06 00:00 [received] PHST- 2014/02/25 00:00 [accepted] PHST- 2014/03/25 06:00 [entrez] PHST- 2014/03/25 06:00 [pubmed] PHST- 2014/11/19 06:00 [medline] PHST- 2014/03/21 00:00 [pmc-release] AID - PONE-D-13-51367 [pii] AID - 10.1371/journal.pone.0092722 [doi] PST - epublish SO - PLoS One. 2014 Mar 21;9(3):e92722. doi: 10.1371/journal.pone.0092722. eCollection 2014.